The association between serum albumin and alkaline phosphatase in cancer patients.

The role of serum albumin (ALB) has been extensively studied in patients with cancer; however, research on its effect on bone metastasis in these patients remains limited. This study aimed to investigate the relationship between serum ALB and alkaline phosphatase (ALP) levels in patients with tumors. Using data from the National Health and Nutrition Examination Survey 2011 to 2018, we assessed the correlation between serum ALB and ALP levels using a weighted multivariate linear regression model, whereas a weighted generalized additive model and smooth curve fitting were used to address potential nonlinearities. A total of 1876 patients with cancer were included in our study. In the subgroup analysis stratified by sex, race/ethnicity, and liver disease, the negative correlation of ALB with ALP remained for most groups, except in blacks (ß = -1.755, 95%CI: [-3.848, 0.338], P = .103) and patients with gout (ß = -0.676, 95%CI: [-2.061, 0.709], P = .340). In black people and patients with gout, the relationship between ALB and ALP showed an inverted U-shaped curve, with an inflection point at approximately 42 g/dL. Our study showed an inverse correlation between ALB and ALP levels in most patients with tumors, but not in black patients and those with gout. The measurement of ALB levels can serve as a screening tool for bone metastases while guiding therapeutic intervention strategies.

A rare malignant mesothelioma of the tunica vaginalis testis: A case report.

Malignant mesothelioma of the tunica vaginalis testis is a rare, highly invasive urogenital malignant tumor with no specific clinical manifestations. Reported cases of this disease are limited. Therefore, an early preoperative diagnosis is difficult. The current study presents a case of malignant mesothelioma of the tunica vaginalis testis and a literature review. A 52-year-old man was admitted to Xiaoshan Affiliated Hospital of Wenzhou Medical University (Hangzhou, China) in December 2022 and underwent radical resection of the right testicle and epididymis but did not undergo radiotherapy or chemotherapy. The patient was followed up for 5 months, and no recurrence or metastasis was found. The rarity of testicular mesothelioma poses a challenge to its etiology and diagnosis, which is rarely achieved preoperatively. Malignant mesothelioma of the testicular tunica vaginalis has a poor prognosis and is not sensitive to radiotherapy or chemotherapy, requiring close postoperative follow-up. This condition is rare in clinical practice; therefore, it needs to be reported to aid clinicians' decision-making regarding diagnosis and treatment.

Identification of L11L and L7L as virulence-related genes in the African swine fever virus genome.

Introduction: African swine fever (ASF) is an infectious disease that causes considerable economic losses in pig farming. The agent of this disease, African swine fever virus (ASFV), is a double-stranded DNA virus with a capsid membrane and a genome that is 170-194 kb in length encoding over 150 proteins. In recent years, several live attenuated strains of ASFV have been studied as vaccine candidates, including the SY18ΔL7-11. This strain features deletion of L7L, L8L, L9R, L10L and L11L genes and was found to exhibit significantly reduced pathogenicity in pigs, suggesting that these five genes play key roles in virulence. Methods: Here, we constructed and evaluated the virulence of ASFV mutations with SY18ΔL7, SY18ΔL8, SY18ΔL9, SY18ΔL10, and SY18ΔL11L. Results: Our findings did not reveal any significant differences in replication efficiency between the single-gene deletion strains and the parental strains. Pigs inoculated with SY18ΔL8L, SY18ΔL9R and SY18ΔL10L exhibited clinical signs similar to those inoculated with the parental strains. Survival rate of pigs inoculated with 103.0TCID50 of SY18ΔL7L was 25%, while all pigs inoculated with 103.0TCID50 of SY18ΔL11L survived, and 50% inoculated with 106.0TCID50 SY18ΔL11L survived. Discussion: The results indicate that L8L, L9R and L10L do not affect ASFV SY18 virulence, while the L7L and L11L are associated with virulence.

The association between albumin and C-reactive protein in older adults.

Albumin had been found to be a marker of inflammation. The purpose of our study was to investigate the relationship between albumin and C-reactive protein (CRP) in 3579 participants aged 60 to 80 years from the National Health and Nutrition Examination Survey (NHANES). In order to evaluate the association between albumin and CRP, We downloaded the analyzed data (2015-2018) from the NHANES in the United States, and the age of study population was limited to 60 to 80 years (n = 4051). After exclusion of subjects with missing albumin (n = 456) and CRP (n = 16) data, 3579 subjects aged 60 to 80 years were reserved for a cross-sectional study. All measures were calculated accounting for NHANES sample weights. We used the weighted χ2 test for categorical variables and the weighted linear regression model for continuous variables to calculate the difference among each group. The subgroup analysis was evaluated through stratified multivariable linear regression models. Fitting smooth curves and generalized additive models were also carried out. We found albumin negatively correlated with CRP after adjusting for other confounders in model 3 (ß = -0.37, 95% CI: -0.45, -0.28, P < .0001). After converting albumin from a continuous variable to a categorical variable (quartiles), albumin level was also negatively associated with serum CRP in all groups (P for trend < .001 for each). In the subgroup analysis stratified by gender, race/ethnicity, smoking, high blood pressure, the negative correlation of albumin with CRP was remained. We also found that the level of CRP further decreased in other race (OR: -0.72, 95% CI: -0.96, -0.47 P < .0001) and participants with smoking (OR: -0.61, 95% CI: -0.86, -0.36 P < .0001). Our findings revealed that albumin levels was negatively associated with CRP levels among in USA elderly. Besides, CRP level decreased faster with increasing albumin level in other race and participants with smoking. Considering this association, hypoalbuminemia could provide a potential predictive biomarker for inflammation. Therefore, studying the relationship between albumin and CRP can provide a screening tool for inflammation to guide therapeutic intervention and avoid excessive correction of patients with inflammation.

Follicular carcinoma originating from struma ovarii: A case report.

INTRODUCTION: Follicular carcinoma originating from struma ovarii is a clinically rare low-grade malignant tumor. The pathological diagnosis of ovarian thyroid follicular carcinoma is predominantly based on the infiltrative growth and vascular involvement of tumor cell nests of different sizes in the ovarian parenchyma. PATIENT CONCERNS: Here we present a case of this malignancy in which the bilateral ovaries, right oviduct wall, myometrial surface, omentum, and bladder reflex were extensively involved Microscopically, the thyroid follicles in this case showed infiltrative growth of nodules of different sizes in the ovarian stroma. DIAGNOSIS: The epithelial layer of the follicles was atypical, but with no nuclear features of papillary thyroid carcinoma such as nuclear groove and nuclear pseudoinclusions. Immunohistochemistry showed positive expression of thyroglobulin, thyroid transcription factor-1, and cytokeratin19, with a Ki-67 index of 5% +. Immunohistochemical results combined with microscopic morphology allowed a diagnosis of follicular carcinoma originating from struma ovarii. INTERVENTIONS: After exclusion of contraindications to surgery, the patient underwent surgical exploration on July 26, 2022, during which frozen pathological examination was performed. OUTCOMES: The patient recovered well and was discharged. At the first follow-up visit in October 2022, the patient had an excellent survival. CONCLUSION: The analysis of the microscopic morphological characteristics and immunohistochemistry deepened our understanding of the pathological characteristics of ovarian and thyroid follicular carcinoma, and further provides a diagnostic reference for other clinicians who will encounter these conditions in the future.

Comprehensive circular RNA expression profile of lung adenocarcinoma with bone metastasis: Identification of potential biomarkers.

Background: Lung adenocarcinoma (LUAD) has a significant tendency to metastasize to the bone, with severe comorbidities. Recent studies have reported that circular RNAs (circRNAs) are involved in various cancer metastasis-related physiological cellular processes. However, their role in LUAD with bone metastasis (LUAD-BM) remains unknown. Methods: Bone metastasis (BM) circRNAs were identified using high-throughput sequencing and validated by quantitative reverse transcription-PCR (qRT-PCR). Bioinformatic analyses were used to predict the potential functions of the differentially expressed circRNAs. The effects of circ_0096442 on the growth and metastasis of A549 cells were detected in a co-culture system of A549 and bone marrow-derived cells. Results: There were 598 (238 upregulated and 360 downregulated) 390 (187 upregulated and 203 downregulated) and 644 (336 upregulated and 308 downregulated) differentially expressed circRNAs between LUAD-BM and LUAD, LUAD-BM and healthy individuals, and LUAD and healthy individuals, respectively. These differentially expressed circRNAs play important roles in cellular components, biological processes, and molecular functions. Moreover, they map several pathways related to BM, including DNA repair, DNA damage, and osteoclast differentiation. The results validated by qRT-PCR for the five most dysregulated circRNAs are consistent with the sequencing data. Additionally, circ_0096442 was found to promote the growth and metastasis of LUAD in a bone microenvironment. Conclusion: Our findings provide a novel and important circRNA expression profile of LUAD-BM and suggest that circ_0096442 may be a biomarker for LUAD-BM.

A first-in-human, phase 1a dose-escalation study of the selective MEK1/2 inhibitor FCN-159 in patients with advanced NRAS-mutant melanoma.

BACKGROUND: A phase 1a first-in-human study evaluated the safety/tolerability, preliminary antitumour activity and pharmacokinetics of the oral MEK1/2 inhibitor FCN-159 in Chinese patients with advanced, NRAS-mutant melanoma. PATIENTS AND METHODS: Patients received a single FCN-159 dose at assigned levels, proceeding to continuous dosing (once daily [QD] for 28-day cycles) if no dose-limiting toxicities (DLTs) occurred within the next 3 days. Dose escalation was initiated after review of data for the previous dose level. The primary end-point was incidence of DLTs after the first dose. RESULTS: Thirty-three patients were enrolled across nine FCN-159 dose groups (0.2-15 mg QD). One DLT occurred: grade 3 folliculitis in the 15-mg group. There was one grade >3 treatment-emergent adverse event (TEAE), death of unknown aetiology (not FCN-159 related). The most common FCN-159-related TEAE was rash (36.4%), and the incidence of grade ≥3 FCN-159-related TEAEs was 15.2%. Antitumour activity at QD doses <6 mg was limited; therefore, efficacy data are presented only for doses ≥6 mg (n = 21). The objective response and clinical benefit rates were 19.0% (four partial responses) and 52.4%, respectively. Median (95% confidence interval) duration of response and progression-free survival were 4.8 months (2.8-not reached) and 3.8 months (1.8-5.6), respectively. FCN-159 exposure increased dose-proportionately; geometric mean terminal half-life was 29.9-56.9 h. CONCLUSIONS: FCN-159 was well tolerated and demonstrated promising antitumour activity at doses ≥6 mg QD in patients with advanced, NRAS-mutant melanoma. The recommended phase 2 dose was 12 mg QD. GOV IDENTIFIER: NCT03932253. https://clinicaltrials.gov/ct2/show/NCT03932253.

Malignant transformation of Warthin's tumor into squamous cell carcinoma: A case report.

Malignant transformation of Warthin's tumor into squamous cell carcinoma is rare. The present study reported on a case of a 67-year-old male patient diagnosed with this condition. Microscopically, the tumor was mainly composed of squamous cell carcinoma and lymphoid stroma. Furthermore, the squamous cell carcinoma cells were arranged in a solid flake-like, papillary and cystic shape. Local bleeding was observed in the mass and a large number of lymphoid stroma-associated centers were observed between the cancer cells. The expression of cytokeratin (CK)5/6, P40, CK7, CK18, CK8 and MutS protein homolog 2 was detected by immunohistochemistry, in addition to Epstein-Barr encoding region in situ hybridization (-), Ki-67 (epithelial 25% +) and p53 (wild-type). The diagnosis of malignant transformation of Warthin's tumor into squamous cell carcinoma depends on the histopathology. The microscopic diagnosis is based on the dynamic process of scaling, atypical hyperplasia and cancerization of the eosinophilic columnar epithelium. Of note, it is also necessary to differentiate it from cervical malignant tumors such as lymphoepithelial carcinoma. The main clinical treatment is surgical resection with negative margins.

Boryl Radical Activation of Benzylic C-OH Bond: Cross-Electrophile Coupling of Free Alcohols and CO2 via Photoredox Catalysis.

A new strategy for the direct cleavage of the C(sp3)-OH bond has been developed via activation of free alcohols with neutral diphenyl boryl radical generated from sodium tetraphenylborate under mild visible light photoredox conditions. This strategy has been verified by cross-electrophile coupling of free alcohols and carbon dioxide for the synthesis of carboxylic acids. Direct transformation of a range of primary, secondary, and tertiary benzyl alcohols to acids has been achieved. Control experiments and computational studies indicate that activation of alcohols with neutral boryl radical undergoes homolysis of the C(sp3)-OH bond, generating alkyl radicals. After reducing the alkyl radical into carbon anion under photoredox conditions, the following carboxylation with CO2 affords the coupling product.

Comparison of surface properties, cell behaviors, bone regeneration and osseointegration between nano tantalum/PEEK composite and nano silicon nitride/PEEK composite.

Both tantalum (Ta) and silicon nitride (SN) exhibit osteogenic bioactivity and antibacterial property. In addition, as a biomaterial for bone repair, polyetheretherketone (PEEK) has outstanding biocompatibility and mechanical performances while it is biologically inert. In this study, by blending PEEK with Ta and SN nanoparticles, respectively, Ta/PEEK composite (TPC) and SN/PEEK composite (SPC) were fabricated for load-bearing bone repair. The surface roughness, hydrophilicity and surface energy of TPC containing Ta nanoparticles were higher than SPC containing SN nanoparticles and PEEK. In addition, TPC with Ta nanoparticles exhibited low antibacterial property while SPC with SN nanoparticles showed high bacterial property. Moreover, the MC3T3-E1 cells responses (e.g. proliferation and differentiation) to TPC was the highest while PEEK was the lowest in vitro. Furthermore, new bone formation and osseointegration for TPC was the highest while PEEK was the lowest in vivo. In conclusion, compared with PEEK, addition of Ta and SN nanoparticles into PEEK fabricated bioactive composites of TPC and SPC with optimized surface property, which played crucial roles in inducing cellular response/bone regeneration. Although the osteogenic activity of SPC was lower than TPC, SPC exhibited osteogenic activity and good antibacterial property, which could prevent infection from bacterial. Therefore, SPC would have better potential for bone substitute.

Small-cell lung cancer transformation from EGFR-mutant adenocarcinoma after EGFR-TKIs resistance: A case report.

RATIONALE: With the recent advancements in molecular biology research, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have emerged as excellent therapies for patients with EGFR-mutant cancers. However, these patients inevitably develop cross-acquired resistance to EGFR-TKIs. Transformation to small-cell lung cancer (SCLC) is considered a rare resistance mechanism against EGFR-TKI therapy. Here, we report a case of TKI resistance due to SCLC transformation and demonstrate its mechanisms and clinical features. PATIENT CONCERNS: A 54-year-old Chinese man with a history of smoking for 40 years complained of an intermittent cough in March 2019. DIAGNOSIS: Transbronchial lung biopsy was performed on the basal segment of the left lower lobe, which confirmed lung adenocarcinoma. In January 2020, repeat biopsy was performed, and the results of immunohistochemistry (IHC) staining showed TTF-1 (+), CK7 (+), napsin A (+), syn (+), and CD56 (+), with a Ki-67 (+) index 80% of small cell carcinomas. Infiltrating adenocarcinomas and small cell carcinomas were observed. INTERVENTIONS: Icotinib (125 mg thrice daily) was administered as a first-line treatment from June 2019. We subsequently administered a chemotherapy regimen consisting of etoposide (180 mg, days 1-3) plus cisplatin (45 mg, days 1-3) every 3 weeks for 1 cycle after recurrence. As the patient could not tolerate further chemotherapy, he continued taking icotinib orally and received whole-brain radiotherapy 10 times to a total dose of 30 Gy after brain metastases. OUTCOMES: The patient relapsed after successful treatment with icotinib for 9 months. A partial response was achieved after 4 cycles of chemotherapy, and despite the brief success of chemotherapy, our patient exhibited brain metastasis and metastases of the eleventh thoracic spine and the second lumbar vertebra with pathological fracture. The patient eventually died of aggressive cancer progression. LESSONS: Our case highlights the possibility of SCLC transformation from EGFR-mutant adenocarcinoma and the importance of repeat biopsy for drug resistance. Serum neuron-specific enolase levels may also be useful for detecting early SCLC transformation.

Poria cocos polysaccharide attenuates damage of nervus in Alzheimer's disease rat model induced by D-galactose and aluminum trichloride.

Poria cocos polysaccharide (PCP) is a compound from Poria cocos, and which is used as a classical tonic agent. This article aims to investigate the effects of PCP on neuronal damage of hippocampus and cognitive function in a rat model of Alzheimer's disease induced by D-galactose and aluminum trichloride. Oxiracetam (ORC) was used as a positive drug in this experiment. The rats were treated with PCP at doses of 100, 200 and 300 mg/kg/day for 30 days and ORC at dose of 346 mg/kg/day after modeling. The results of behavioral test showed that PCP could prevent cognitive decline in Alzheimer's disease rats as assessed by Y-maze test and Morris water maze test. Results of hippocampus slices showed that neurons were integrated and regularly arranged in the groups, which were administered along with PCP. Moreover, PCP could reduce neuronal apoptosis in hippocampus of Alzheimer's disease rats. Furthermore, the activities of superoxide dismutase in the hippocampus were elevated by PCP administration, while acetyl cholinesterase, reactive oxygen, malondialdehyde and inflammatory factors levels were reduced. In addition, we found PCP could attenuate MAPK/NF-κB signal pathway in the hippocampus. All results illustrated that PCP could exert neuroprotective effects at least partly through alleviating oxidative stress, apoptosis, inflammation and inhibiting the MAPK/NF-κB pathway in Alzheimer's disease rats induced by D-galactose and aluminum trichloride.

Factors affecting thyroid volume in adolescent students attending a rural middle school in East Hangzhou, China.

OBJECTIVE: To investigate the thyroid volume (Tvol) and to explore factors that affects it among 12 to 15-year-olds attending a rural middle school in east Hangzhou, China. METHODS: A cross-sectional survey of middle school students attending a rural middle school in east Hangzhou, China was conducted. Height, weight and other physical development related indicators in middle school students were measured. The thyroid size was measured using ultrasound, and the thyroid volume calculated. RESULTS: The median (P25, P75) of the thyroid volume in 596 middle school students from a rural middle school in east Hangzhou, China was 6.69 (5.66, 7.98) mL. Our study enrolled 305 male students (51.2%) and 291 female students (48.8%). The height, weight and thyroid volume of middle school students increased with age. Univariate analysis revealed that height, weight, body mass index (BMI) and body surface area (BSA) were positive correlated with thyroid volume (p<0.01).The correlation between BSA and thyroid volume was significant (Spearman's rho=0.473, p<0.01). Multiple linear regression analysis revealed that BSA was positive and significantly correlated with the thyroid volume (p<0.05). Regression equation was Y=-2.532 + 6.186×BSA. CONCLUSION: The thyroid volume is not only affected by age, but it is also affected by growth and development. Goiter cannot only be assessed based on age, gender and thyroid volume. However, this study established that BSA not only presented the strongest correlation with thyroid volume (Spearman's rho=0.473), but also had a strong correlation with physical development, taking into account the growth and development of middle school students, and showed greater stability. Therefore, we recommend inclusion of BSA as a reference standard in the measurement of the thyroid volume.

Evaluation of therapeutic effect of transcutaneous electrical acupoint stimulation on bone metastasis pain and its influence on immune function of patients.

BACKGROUND: This study aimed to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on bone metastasis pain, anxiety and immune function in cancer patients. METHODS: A total of 127 patients with bone metastasis pain from malignant tumors were treated with TEAS or drugs. The TEAS group comprised of 62 patients, while the drug control group comprised of 65 patients. The differences in general indexes, baseline pain and anxiety between these two groups were not statistically significant. RESULTS: Compared with those before treatment, the visual analog scale (VAS) scores of patients in the TEAS group and drug control group decreased after treatment, and the differences were statistically significant. The degrees of pain relief after treatment were similar between the two groups. Anxiety improved in both the TEAS group and drug control group, and the difference between these two groups was not statistically significant. The differences in immune indexes, B cell and CD8 between the TEAS group and drug control group were statistically significant. TEAS treatment could improve the declining trend of CD8 in patients. CONCLUSIONS: TEAS treatment and drug treatment can effectively alleviate mild to moderate pain in patients, and the efficacy of these two groups is similar. The treatment for moderate and severe pain needs to be combined with drug treatment to achieve a control effect. TEAS can improve the anxiety and immune function of patients, and prevent the decrease in B cells and CD8 in patients treated with drugs alone.

[Effect of microRNA-29b on proliferation and migration of breast cancer cells and its molecular mechanism].

OBJECTIVE: To investigate the effects of microRNA(miRNA)-29b on the proliferation and migration of breast cancer cells and its molecular mechanism. METHODS: The recombinant lentiviral expression vector (lenti-miRNA-29b) was constructed and transfected into 293T cells to obtain lentivirus particles that were used to infect breast cancer MCF-7 cells. Transfection efficiency of lenti-miRNA-29b in MCF-7 cells was identified by the expression of green fluorescent protein (GFP). The expression of miRNA-29b was detected by real-time PCR. The cell proliferation and migration were detected by CCK8 assay and Transwell assay, respectively. The bioinformatics softwares were used to predict and screen the downstream target genes regulated by miRNA-29b, which were verified by double luciferase reporter gene assay, RT-PCR and Western blot. The effects of screened target gene RTKN on the growth and migration of MCF-7 cells were verified by RTKN siRNA. RESULTS: Recombinant lentiviral expression vector of miRNA-29b were successfully constructed. About 90% and 60% of the breast cancer cells showed green fluorescence in lenti-miRNA-29b and lenti-miRNA-NC groups, respectively. The expression of miRNA-29b in lenti-miRNA-29b group increased significantly compared with the lenti-miRNA-NC group and blank control group (all P<0.05); the proliferation and migration ability of MCF-7 cells significantly reduced compared with the control group (all P<0.05). The screening with bioinformatics softwares found that the 3'UTR coding region RTKN had the binding site to miRNA-29b; the dual luciferase reporter gene assay showed that the luciferase activity decreased significantly after the MCF-7 cells were co-transfected with wild type RTKN-WT-3'UTR and miRNA-29b mimics report gene vector (P<0.05). The RTKN proteins in MCF-7 cells were significantly decreased after transfection with siRNA-RTKN, and the proliferation and migration ability of MCF-7 cells were significantly reduced (all P<0.05). CONCLUSIONS: MiRNA-29b can inhibit the proliferation, invasion and metastasis of breast cancer cells by inhibiting the expression of RTKN.

Downregulation of caveolin-1 increases the sensitivity of drug-resistant colorectal cancer HCT116 cells to 5-fluorouracil.

Colorectal cancer is the third most common type of cancer in men and women. Chemotherapy is an important treatment strategy for patients with terminal stage cancer. However, the development of drug resistance hampers the effectiveness of chemotherapy. Therefore, an effective therapeutic approach to target chemoresistance-associated cellular molecules is required. In the present study, drug-resistant human colorectal cancer HCT116 cells were developed by treating HCT116 cells with increasing concentrations of 5-fluorouracil (5-FU). The present study indicated that the drug-resistance cells (DRC) were resistant to 5-FU compared with parental HCT116 cells by detecting cell survival using an MTT assay. Additionally, the expression of the chemoresistance-associated protein caveolin-1 (Cav-1) was assessed by reverse transcription-quantitative polymerase chain reaction and western blotting. The results revealed that the Cav-1 expression level was significantly higher in DRC compared with that in the parental HCT116 cells. Next, Cav-1 was silenced by small interfering RNA (siRNA) or was inhibited with its specific inhibitor methyl ß-cyclodextrin (MCD). MTT assay demonstrated that Cav-1 siRNA and MCD resensitized DRC to 5-FU. These data reveal that Cav-1 was involved in the development of resistance, suggesting that Cav-1 is a potential target for the treatment of colorectal cancer chemoresistance. In addition, 5-FU combined with Cav-1 siRNA or its specific inhibitor may increase the effectiveness of the treatment strategy.

Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress.

Here we explored the anti-oxidative and cytoprotective potentials of escin, a natural triterpene-saponin, against hydrogen peroxide (H2O2) in retinal pigment epithelium (RPE) cells. We showed that escin remarkably attenuated H2O2-induced death and apoptosis of established (ARPE-19) and primary murine RPE cells. Meanwhile, ROS production and lipid peroxidation by H2O2 were remarkably inhibited by escin. Escin treatment in RPE cells resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by transcription of anti-oxidant-responsive element (ARE)-regulated genes, including HO-1, NQO-1 and SRXN-1. Knockdown of Nrf2 through targeted shRNAs/siRNAs alleviated escin-mediated ARE gene transcription, and almost abolished escin-mediated anti-oxidant activity and RPE cytoprotection against H2O2. Reversely, escin was more potent against H2O2 damages in Nrf2-over-expressed ARPE-19 cells. Further studies showed that escin-induced Nrf2 activation in RPE cells required AKT signaling. AKT inhibitors (LY294002 and perifosine) blocked escin-induced AKT activation, and dramatically inhibited Nrf2 phosphorylation, its cytosol accumulation and nuclear translocation in RPE cells. Escin-induced RPE cytoprotection against H2O2 was also alleviated by the AKT inhibitors. Together, these results demonstrate that escin protects RPE cells from oxidative stress possibly through activating AKT-Nrf2 signaling.

Anticancer activities of anti-membrane antibodies against colon carcinoma cells undergoing chemotherapy.

AIMS AND BACKGROUND: Chemotherapy combined with target therapy using antibodies against tumor cell membrane antigens may greatly increase the survival of cancer patients. Similar to autoantigens in autoimmunity diseases, certain membrane components may be more heterogeneous and create new determinants of antigens or haptens after chemotherapy. The aim of the current study was to prepare anti-membrane antibodies against colon carcinoma cells undergoing chemotherapy and examine their anticancer activities in vitro. METHODS: After the colon carcinoma cells were treated by mimic chemotherapy, the synthesized poly-lysine was used as a carrier to link the membrane antigen or hapten with the covalent bond of carbodiimide bridging. It was affirmed by fluorescence-activated cell sorting under laser confocal microscopy that the vaccine with poly-lysine membrane-linked cells with a covalent bond was successfully engineered. Then, the cognate mice were vaccinated, and the anti-membrane polyclonal antibodies were prepared and validated for their activities. RESULTS: The anti-membrane polyclonal antibodies were effectively induced and prepared. Folliculus lymphaticus were found significantly increased in vaccinated mice, and B lymphocyte proliferation was also intensively stimulated by vaccine and generating antibodies. The polyclonal antibodies, exhibiting minimal endotoxicity, displayed intensive sensitivity, high affinity and strong specificity. They also elicited apoptosis and necrosis for wild type colon carcinoma cells and offered synergistic effect to repress the chemotherapy-resistant tumor cells. CONCLUSIONS: The poly-lysine-linked membrane for colon carcinoma cells undergoing chemotherapy could produce the anti-membrane polyclonal antibodies (promising as novel antibody molecules for target therapy) and generate an effective immune attack on the surviving cancer cells.

Effects of sequential chemotherapy of FOLFIRI/FOLFOX on the endocrine axes of ACTH-cortisol and renin-angiotensin-aldosterone.

The chemotherapies of FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) and FOLFIRI (folinic acid + 5-fluorouracil + irinotecan) are effective for a variety of malignant tumors. In particular, the sequential chemotherapy of FOLFOX/FOLFIRI has become the preferred post-operational treatment approach for gastrointestinal cancer and an important palliative care program for advanced cancer. However, the sequential chemotherapy of FOLFOX/FOLFIRI showed severe side effects due to the fact that the toxicity of the drugs can be enhanced by each other. Here, we report the dynamic changes in the activities of serum ACTH, cortisol, renin, angiotensin, and aldosterone in patients following multiple cycles of FOLFOX/FOLFIRI sequential chemotherapy. We found that the sequential chemotherapy might cause damage to the activities of the endocrine cells and/or the sympathetic nerve, and alter endocrine function, specifically the ACTH-cortisol and renin-angiotensin-aldosterone axes.